High Grade Non Research Articles

Increased Risk for Thromboembolism Associated with High Coagulation Factor VIII (F VIII) Levels in Patients with Malignant Lymphoma.

An increased annual incidence of thromboembolic events (TE) of up to 11% has been observed in patients with solid tumors, whereas there exists little data on TE in hematologic malignancies. A previous study found a 6,6% incidence of TE in patients with high grade Non Hodgkin's lymphoma (HG-NHL) mostly occuring during the first three months of therapy. Little is known about pathogenesis and risk factors in this patient group. We retrospectively evaluated the medical records of all patients with malignant lymphoma treated at our institution between 1991 and 2004. In a seperate effort laboratory analysis for detection of acquired and hereditary thrombophilia was performed at diagnosis and during treatment in 44 patients with various hematologic malignancies: HG-NHL (n = 22), Low grade- NHL (LG-NHL) (n = 7), Hodgkin's disease (HD) (n = 6), CNS-lymphoma (n = 1) and acute myeloid leukemia (AML) (n = 8). A total of 96 TE occurred in 80 of 1048 patients (7,6%) with malignant lymphoma: DVT (n = 51), pulmonary embolism (n = 19), central venous catheter thrombosis (n = 11), upper extremity thrombosis due to tumor compression (n = 9), central nervous system thrombosis (n = 3), arterial thrombosis (n = 2) and portal vein thrombosis (n = 1). 69 TE (72%) occurred during treatment, whereas 27 (28%) were diagnosed prior to (n = 16) (17%) or after completion of therapy (n = 11) (11%). 9 patients (9%) had comorbid solid tumors. In 12 patients (15%) results of thrombophilia screening were available and FVIII levels were high (> 150%) in 7 (58%). In the prospectively analyzed patient cohort 30 (68%) had high FVIII levels, 22 (50%) showing very high levels (> 180%). High FVIII was associated with high von Willebrand factor (vWF) and increased collagen binding activity, but not with elevated IL 6 or TNF-a. 4 patients (9%) had heterozygous factor V Leiden mutation, one had the G20210A mutation of the prothrombin gene. Fibrinolysis was normal in all patients as were protein C, S and AT-III. No anticardiolipin antibodies or lupus anticoagulants were detected. However only 2 patients (4,4%) in this cohort developed TE, one of whom also had heterozygous protein C resistance. Patients with malignant lymphoma are at substantial risk for TE, especially during treatment, thus prophylactic anticoagulation seems warranted. Our study shows sustained strikingly high factor VIII levels in patients with malignant lymphoma even months or years after a TE as well as in a prospectively analyzed, yet mostly asymptomatic cohort with lymphoma and acute leukemia. Infection as a cause of secondary F VIII elevation in these patients was ruled out by absence of fever and normal IL 6 and TNF-a. Increased FVIII activity (> 150%) has been recognized as an independent risk factor for TE, however the pathogenesis is unclear so far and high FVIII and vWF levels have previously also been found in Multiple Myeloma patients. Ongoing investigations will focus on the implication of these findings in the pathophysiology of hematologic disease.

Intermediate and High Grade Non Hodgkin's Lymphoma in the Elderly

Many malignant tumors develop in the later years of life. One of malignancies that frequently occurs in older patients is non Hodgkin's lymphoma (NHL) with a median age at diagnosis over 60 years. The overall incidence of NHL has increased over the past decade and is expected to continue to rise in developed countries. So NHL will be diagnosed more in the future. In this review we discuss epidemiology, etiology, possible differences in tumor characteristics compared with younger NHL patients, treatment and treatment results in elderly NHL patients.

Intensification of the CHOEP Regimen for High-Grade Non- Hodgkin’s Lymphoma by G-CSF: Feasibility of a 14-Day Regimen

<i>Background</i>: The efficacy of chemotherapy protocols for the treatment of high-grade non-Hodgkin’s lymphoma (NHL) has not improved significantly during the last decade. Treatment results in patients presenting with high-grade NHL are not satisfactory. At present, etoposide remains the only drug that may add to the efficacy of the CHOP regimen. Hemopoietic growth factors like G-CSF allow a dose intensification of effective chemotherapy regimens by shortening the time of neutro-penia and allowing earlier application of subsequent cycles. We have initiated a phase I/II trial of CHOP + etoposide (CHOEP) applied in 14-day intervals with G-CSF support to test the feasibility of this regimen before starting a trial comparing its efficacy with the more conventional regimens. <i>Patients and Methods</i>: Patients with high-grade NHL according to the Kiel classification were treated with the CHOEP-14 regimen, consisting of cyclophosphamide (750 mg/m2 i.v., day 1), doxorubicin (50 mg/m2, day 1), vincristine (2 mg i.v., day 1), etoposide (100 mg/m2, days 1-3) and prednisolone (100 mg p.o., days 1-5). G-CSF, 300 μg (up to 75 kg body weight) or 480 μg was applied s.c. (days 4-13). Cycles were repeated on day 15 and patients received 6 cycles followed by irradiation of bulky disease with 36 Gy. <i>Results</i>: To date, 30 patients with high-grade NHL (median age 55 years, range 25-79 years) have been treated for a total of 159 evaluable chemotherapy cycles. 24 patients have finished 6 cycles each, and 20 patients are evaluable for response. Application of the following cycle was on day 15 in 146/159 cycles, and delay in 16 cycles (duration between 1 and 13 days) was not caused by ncutro-penia in any patient. Leucopenia < 1,000/mm3 occurred in 18/159 cycles, but never lasted longer than 4 days. White blood cell counts recovered completely by day 14 in all cycles. Toxicity was tolerable and never exceeded WHO grade 3. A complete remission (CR) was observed in 17/20 patients, a partial remission (PR) in 2/20 patients before radiation therapy. One patient died due to disease progression (cerebral involvement). <i>Conclusion</i>: Dose intensification of the standard CHOP regimen by addition of etoposide and implementation of 14-day cycles with growth factor support is possible without undue increase in treatment toxicity. A randomized multicenter phase III trial has been initiated to test whether this significant increment in dose intensity translates into increased remission rates and/or longer remission durations.